Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is much experimental data which indicates that ionizing radiation is a very potent carcinogenic agent. Most types of carcinoma can be produced by radiation. Carcinoma is apparently induced through a single or a series of mutations in somatic cells. Radiologists have excess leukemia and other malignancy from external x-ray; uranium and other miners have excess lung cancer from internal alpha radiation; luminous dial painters have excess osteogenic sarcomas; and uranium mill workers appear to have excess lymphomas. A large number of persons are now exposed occupationally to radiation from nuclear reactors, and from various uses of radioisotopes. For the induction of most types of cancers from radiation it appears that the risk is between 0.5 and 2 cancers per rem per million person years. Epidemiological techniques are essential in determining risks of this low magnitude. Other agents may inhibit or enhance the carcinogenicity of radiation.
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PMID:Occupational exposure to radiation as a cancer hazard. 32 45

Osteoblasts, members of the marrow stromal cellular network, may play an active role in the hemopoietic microenvironment as well as in bone remodeling. In this study, we examined the extent to which marrow-derived osteogenic cells (MBA-15) possess various stromal functions. This marrow stromal-derived cell line was shown by us to exhibit osteoblastic characteristics in culture and to form bone in vivo. These cells are shown here to constitutively produce and secrete cytokines identified as M-CSF, GM-CSF, and IL-6. MBA-15 cells modulate growth of normal and malignant myeloid and lymphoid cells as well as leukemia cell lines in vitro. Cell-cell interactions were studied in co-cultures with adherent MBA-15 cells and the target hemopoietic cells. Growth inhibition effects, observed under various experimental conditions, can be attributed to the presence of different soluble and membrane-bound inhibitory activities produced by MBA-15 cells. Thus, MBA-15 cells spontaneously produce both stimulators and inhibitors that can affect myeloid and lymphoid cell growth. Marrow osteogenic cells may therefore participate in the stromal regulation of hemopoiesis.
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PMID:Hemopoietic functions of marrow-derived osteogenic cells. 142 64

The carcinogenic effects of cadmium have not been thoroughly assessed in the commonly used Fischer (F344) rat. This study determined tumor incidence in various tissues of male F344/NCr rats after a single dose of cadmium. Cadmium (as CdCl2) was given sc in the dorsal thoracic midline at 30 mumole/kg to 70 8-week old male F344 rats while controls (n = 50) received saline. Rats were observed during the next 90 weeks. Early deaths (less than or equal to 32 weeks), due mostly to acute cadmium-induced hepatotoxicity, accounted for 37 of the cadmium-treated rats while no control rats died in the same period. A high incidence of injection site sarcomas (ISS) occurred in the cadmium-treated group (21 ISS/32 rats at risk; 66%) while only 1/50 occurred in controls (2%). In fact, ISS were the major cause of morbidity after 35 weeks in cadmium-treated rats. These tumors were mostly fibrosarcomas, although histiocytic and osteogenic sarcomas also occurred. Testicular interstitial cell tumors, which show a very high spontaneous incidence in this strain (41/49; 84%), were not markedly affected by cadmium (30/31; 97%). This is in sharp contrast to other strains, such as the Wistar, in which cadmium treatment is reported to cause as much as an eightfold increase in interstitial cell (Leydig cell) tumor incidence. The incidence of large granular lymphocyte (LGL) leukemia, which also occurred frequently in control F344 rats (12/47; 26%) was markedly decreased (2/31; 7%) by cadmium. Our recent studies indicate acute lymphonecrotic effects occur with cadmium in lymphoid tissues of rats, and this may be related to the suppression of the leukemia. These results indicate that cadmium is very effective in inducing ISS in F344 rats, as is the case with other strains thus far tested, and also markedly reduces spontaneous leukemia incidence.
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PMID:Chronic carcinogenic and toxic effects of a single subcutaneous dose of cadmium in the male Fischer rat. 185 89

CI-940, PD 114,721, and PD 118,607 are structurally novel antibiotics, which were isolated from fermentation beers of a previously unknown actinomycete. They are highly lipophilic acids characterized by unsaturated lactone and branched, polyunsaturated aliphatic side-chain moieties. All three agents demonstrated significant cytotoxic activity in vitro against a number of human and mouse tumor lines which encompassed a wide range of tissue types. CI-940 retained full activity in vitro against lines of P388 leukemia that are resistant to Adriamycin, amsacrine, and mitoxantrone. Activity was confirmed for both CI-940 and PD 114,721 against a number of murine experimental tumor systems in vivo, which included the P388 and L1210 leukemias and also B16 melanoma, Ridgway osteogenic and M5076 sarcomas, and mammary adenocarcinoma 16/C. PD 118,607 was also highly active against B16 melanoma. All three agents demonstrated anticancer activity at very low dosages compared with current clinically useful anticancer agents. No significant activity was seen against the MX-1 human mammary xenograft or pancreas 02 tumor models. The primary target for host toxicity of CI-940 and PD 114,721 appeared to be gastrointestinal in nature. Neither CI-940 nor PD 114,721 caused delayed lethality when given either IP or IV. In schedule studies, the toxicities of both CI-940 and PD 114,721 were moderately dependent on the regimen used, with total maximum tolerated dosages for intermittent (q4dx2), daily (qdx5), and divided daily (q4hx3, qdx5) dosing schedules of 1, 0.25, and 0.12 mg/kg, respectively. CI-940 is being developed for clinical trial on the basis of its potent activity against seven different tumor models, its novel structure, and its apparently novel mechanism of action.
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PMID:In vivo and in vitro anticancer activity of the structurally novel and highly potent antibiotic CI-940 and its hydroxy analog (PD 114,721). 308 Dec 69

Five clonal cell lines were established from a spontaneous BALB/c mouse osteosarcoma, and characterized. Four of these lines showed some similarities in morphology, in vitro growth properties, production of collagenous and noncollagenous extracellular matrix proteins and osteogenic differentiation. The cells formed colonies with characteristic differences in size and morphology in soft agar, and osteogenic sarcomas and metastases in syngeneic mice after transplantation. Ultrastructurally, cells in the transplant tumours showed marked osteogenic features. There were no osteoclast-like cells. The fifth cell line had somewhat different characteristics. All five lines expressed infectious endogenous murine leukemia viruses. Increased c-myc protoon-cogene expression was found in one cell line and c-fos expression at different levels in all lines. There was only very low expression of c-Ha-ras and no expression of c-Ki-ras and c-sis. DNA analysis showed the presence of newly acquired proviral genomes integrated at different sites in the cellular DNA. The results show that distinct osteogenic neoplastic subclones can be obtained from a primary mouse osteosarcoma. Although the clones exhibited an appreciable morphological, functional, and molecular diversity they retained the basic pathogenic properties of the tumour from which they were derived.
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PMID:Establishment and characterization of osteogenic cell lines from a spontaneous murine osteosarcoma. 324 85

Leukemia, lymphoma, and osteogenic and anaplastic sarcomas develop in Syrian golden hamsters inoculated intravenously at 3 weeks of age with simian virus 40, which is a popova virus. Previously, only RNA and herpes DNA viruses have been recognized as capable of inducing leukemia and lymphoma in mammals. The significance of these findings is emphasized in relation to the nature of viral agents that may be involved in analogous diseases of man.
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PMID:Leukemia, lymphoma, and osteosarcoma induced in the Syrian golden hamster by simian virus 40. 433 86

Transfection is a technique for inducing transformation of normal fibroblasts (NIH 3T3) with DNA (oncogenes) from human tumors. Our goal was to determine if these transformed cells expressed antigens associated with malignancy. NIH 3T3 cells were transfected with DNA fragments from a human acute lymphocytic leukemia (ALL 1-69), and transformed colonies were selected for growth in soft agar. Transfected cells containing human DNA sequences demonstrated by Southern blot analysis were used to immunize Balb/C mice. Monoclonal antibodies were produced and screened for binding to the parental leukemia (ALL 1-69), transfectant (17(2], and 3T3 cells in an enzyme-linked assay. A monoclonal antibody (IgM kappa) designated 17-9H3 bound to ALL 1-69 and secondary transfectant 17(2) but not to NIH 3T3 plasma membranes. Immunoperoxidase staining confirmed this binding pattern and demonstrated that the antigen was expressed on the cell surface. Expression of the antigen by transfectants directly correlated with the presence of a single 6.1 kilobase human DNA sequence. The antibody binding site of the antigen was inactivated by trypsin, glucosidase, and hyaluronidase. Binding of the 17-9H3 antibody was selective for acute lymphocytic leukemias (5/8) and osteogenic sarcomas (33/36), although other tumor types did demonstrate significant binding by immunoperoxidase staining. The majority of normal tissues did not bind 17-9H3 with the exception of some metabolically active cells (renal tubular epithelium, secretory epithelial cells, and cardiac smooth muscle), germ cells, Leydig cells of the testes, and some lymphoid cells. Monoclonal antibodies to oncogene-associated antigens may be potentially useful for cancer diagnosis and therapy and as probes for oncogene isolation.
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PMID:A novel approach to production of antitumor monoclonal antibodies: antibody to a cell surface glycoprotein associated with transformation by a human oncogene. 637 59

Late biological effects of radium deposited in the human skeleton have manifested themselves unequivocally as osteogenic sarcomas or carcinomas of the mastoid air cells or paranasal sinuses. On the basis of current estimated risk factors, it might be expected that an excess of certain other malignancies could occur in a population of the size of the group exposed to radium (some 3500 cases located, which more than 2000 have measured 226Ra and 228Ra burdens), compared with the incidence in the population at large. An increased incidence of breast cancer has already been reported in female dial workers and it was related to the initial radium intake. On the other hand, very little information is available on the induction of leukaemia by alpha-radiation in human bone marrow. This paper therefore reports an investigation of the incidence of leukaemia among the radium workers. This covers a very wide range of radium burdens and has been done in the light of reasonable estimates of the mean alpha-particle dose received by the skeletal haemopoietic marrow. The number of leukaemia cases is identified and compared with (a) the expected number in a comparable population of the same size and age distribution and (b) predictions based on the risk factor proposed for protection purposes by the ICRP and on the estimated bone marrow doses.
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PMID:Leukaemia incidence in the U.S. dial workers. 657 2

Prostate tumor cells preferentially metastasize to bony sites and lymph nodes at a frequency in excess of that which would be predicted by random tumor cell dissemination. In order to determine whether chemoattractants in these organs promote organ-specific metastasis, we utilized human cell lines derived from and/or related to these organs as sources of potential chemoattractants. Secretory proteins derived from the cell lines MG-63 (osteosarcoma), SK-ES-1 (Ewing's sarcoma), and KG-1 (leukemia) stimulated chemomigration of the TSU-pr1 prostate tumor cells in a dose-dependent manner in Boyden chambers. In addition, secretory proteins from a human prostatic stromal cell line (hPS) and from the TSU-Pr1 prostate tumor cell line were also able to stimulate chemomigration of the TSU-pr1 cells through Boyden chambers. Since lymph nodes and bony sites represent organs of hematopoietic/lymphoid proliferation and activation, we undertook identification of specific cytokines present at these sites which may promote the chemomigration of prostate tumor cells. In this context, the cytokines interleukin-1 alpha, interleukin-2, interleukin-6, tumor necrosis factor-beta, transforming growth factor-beta, interferon alpha 2-a, and granulocyte-macrophage colony-stimulating factor did not stimulate chemomigration of the TSU-pr1 prostate tumor cell line. In contrast, the cytokine epidermal growth factor (EGF) stimulated chemomigration of the TSU-pr1 prostate tumor cells through the Boyden chambers in a dose-dependent manner. Western blot analysis of secretory proteins from the cell lines KG-1, SK-ES-1, MG-63, hPS, and TSU-pr1 identified EGF-immunoreactive proteins in all cases. In addition, EGF immunoreactivity was localized to the stroma of the human prostate, the osteogenic stroma of pelvic medullary bone, and the stroma within the capsule and trabeculae of pelvic lymph nodes. Hence, these results demonstrate that the cytokine EGF promotes the chemomigration of the TSU-pr1 prostate tumor cell line, and that EGF within the stroma of pelvic lymph nodes and medullary bone may act as a chemoattractant for prostate tumor cells, thereby facilitating the preferential formation of metastatic foci within these organs.
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PMID:Epidermal growth factor (EGF) promotes chemomigration of a human prostate tumor cell line, and EGF immunoreactive proteins are present at sites of metastasis in the stroma of lymph nodes and medullary bone. 854 75

The cell surface receptor for gibbon ape leukemia virus (Glvr-1) was recently demonstrated to serve normal cellular functions as a sodium-dependent phosphate (NaPi) transporter. This protein belongs to a newly identified phosphate transporter/retrovirus receptor gene family distinct from renal type I and II NaPi transporters. Although inorganic phosphate (Pi) transport is an important function of osteoblasts and of the matrix vesicles produced by these cells in the context of bone matrix calcification, the molecular identity of the NaPi transport system(s) present in this cell type is still unknown. In contrast to Pi uptake mediated by renal NaPi transporters, the activities of both the osteoblastic transport system and Glvr-1 are decreased at alkaline pH, and this observation led us to investigate expression of this transporter in human SaOS-2 osteosarcoma cells. Northern blotting analysis revealed the presence of a 4-kilobase Glvr-1 transcript. The expression of Glvr-1 messenger RNA (mRNA) was increased in response to insulin-like growth factor I (IGF-I). Associated with this effect, a selective, dose- and time-dependent stimulation of NaPi transport was observed. Actinomycin D and cycloheximide abolished the increase in NaPi transport, which thus appeared to be dependent on RNA and protein synthesis. The increase in Glvr-1 mRNA induced by IGF-I was dose dependent and transient, peaking after 4 h (approximately 4-fold increase in response to 10(-7) M IGF-I). It preceded the maximal expression of NaPi transport stimulation (173-235% of control), which was observed after 18-24 h. Induction of Glvr-1 mRNA expression by IGF-I was inhibited by actinomycin D, suggesting that this effect was related to an increase in gene transcription. The stability of Glvr-1 mRNA was not altered by IGF-I, and Glvr-1 mRNA induction did not require the synthesis of new proteins. These data demonstrate for the first time regulated expression of mRNA encoding the type III NaPi transporter Glvr-1 in osteoblast-like cells. They also suggest that this new transporter family may be involved in Pi handling in osteogenic cells and in its regulation by osteotropic factors.
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PMID:Expression of a newly identified phosphate transporter/retrovirus receptor in human SaOS-2 osteoblast-like cells and its regulation by insulin-like growth factor I. 938 2


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